The objective of this research is to examine the role of insulin and glucagon receptors in disorders of glucose metabolism. In human studies we have examined the relation between insulin binding to monocytes and in vivo insulin sensitivity as determined by the insulin clamp technique. In these studies we found that non-obese maturity-onset diabetic subjects have decreased insulin binding to monocytes which correlates well with impaired insulin sensitivity in these subjects. In other studies we observed that acute exercise in normal man increases insulin binding to monocyte, suggesting that changes in insulin binding may contribute to exercise-induced augmentation in insulin sensitivity. Regarding the hepatic glucagon receptor, we observed that dexamethasone treatment results in increase in glucagon binding to rat liver membranes, which may contribute to the steroid-induced hypersensitivity to glucagon. Recently we developed a sensitive in vitro system to examine the glucagon receptor function employing adult rat hepatocytes in primary monolayer culture.